Retrosplenial cortex (RSC) is a brain region involved in neuropsychiatric and neurodegenerative disorders. It has reciprocal connections with a diverse set of cortical and subcortical brain regions, but the afferent structure and behavioral function of circuits defined by its projection-specific sub-populations have yet to be determined. The corticocortical connections between RSC and secondary motor cortex (M2), as well as corticothalamic connections between RSC and anterodorsal thalamus (AD) have been hypothesized to function as semi-independent, but parallel pathways that impact spatial information processing in distinct ways. We used retrograde and anterograde viral tracers and monosynaptic retrograde rabies virus to quantitatively characterize and compare the afferent and efferent distributions of retrosplenial neuron sub-populations projecting to M2 and AD. AD-projecting and M2-projecting RSC neurons overlap in their collateral projections to other brain regions, but not in their projections to M2 and AD, respectively. Compared with AD-projecting RSC neurons, M2-projecting RSC neurons received much greater afferent input from the dorsal subiculum, AD, lateral dorsal and lateral posterior thalamus, and somatosensory cortex. AD-projecting RSC neurons received greater input from the anterior cingulate cortex and medial septum. We performed chemogenetic inhibition of M2- and AD-projecting RSC neurons and examined its impact on object-location memory, object-recognition, open-field exploration, and place-action association. Our findings indicate that inhibition of M2-projecting RSC neurons impairs object location memory as well as place-action association, while the RSC to AD pathway impacts only object-location memory. The findings indicate that RSC is composed of semi-independent circuits distinguishable by their afferent/efferent distributions and differing in the cognitive functions to which they contribute.

脾后皮层 （RSC） 是参与神经精神和神经退行性疾病的大脑区域。它与不同的皮层和皮层下大脑区域有相互连接，但由其投射特异性亚群定义的回路的传入结构和行为功能尚未确定。RSC 和次级运动皮层 （M2） 之间的皮质皮质连接，以及 RSC 和前背丘脑 （AD） 之间的皮质丘脑连接已被假设为半独立但平行的途径，以不同的方式影响空间信息处理。我们使用逆行和顺行病毒示踪剂以及单突触逆行狂犬病病毒来定量表征和比较投射到 M2 和 AD 的脾后神经元亚群的传入和传出分布。AD 投射和 M2 投射 RSC 神经元在它们与其他大脑区域的侧支投射中重叠，但在它们分别投射到 M2 和 AD 上没有重叠。与 AD 投射的 RSC 神经元相比，M2 投射的 RSC 神经元从背下、AD、外侧背侧和外侧后丘脑以及体感皮层接收到更大的传入输入。AD 投射的 RSC 神经元从前扣带皮层和内侧隔膜接收到更大的输入。我们对 M2 和 AD 投射的 RSC 神经元进行了化学遗传学抑制，并检查了其对对象位置记忆、对象识别、旷场探索和位置操作关联的影响。我们的研究结果表明，抑制 M2 投射的 RSC 神经元会损害对象位置记忆以及位置-动作关联，而 RSC 到 AD 通路仅影响对象位置记忆。 研究结果表明，RSC 由半独立的回路组成，这些回路可通过它们的传入/传出分布来区分，并且它们所贡献的认知功能不同。